Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
J Cell Mol Med. 2019 Feb;23(2):1116-1127. doi: 10.1111/jcmm.14012. Epub 2018 Nov 18.
As a key transcription factor required for bone formation, osterix (OSX) has been reported to be overexpressed in various cancers, however, its roles in breast cancer progression remain poorly understood. In this study, we demonstrated that OSX was highly expressed in metastatic breast cancer cells. Moreover, it could upregulate the expression of S100 calcium binding protein A4 (S100A4) and potentiate breast cancer cell migration and tumor angiogenesis in vitro and in vivo. Importantly, inhibition of S100A4 impaired OSX-induced cell migration and capillary-like tube formation. Restored S100A4 expression rescued OSX-short hairpin RNA-suppressed cell migration and capillary-like tube formation. Moreover, the expression levels of OSX and S100A4 correlated significantly in human breast tumors. Our study suggested that OSX acts as an oncogenic driver in cell migration and tumor angiogenesis, and may serve as a potential therapeutic target for human breast cancer treatment.
作为成骨所必需的关键转录因子，成骨特异性转录因子 2（osterix，OSX）已被报道在多种癌症中过表达，但其在乳腺癌进展中的作用仍知之甚少。在本研究中，我们证实 OSX 在转移性乳腺癌细胞中高表达。此外，它可以上调 S100 钙结合蛋白 A4（S100A4）的表达，并增强乳腺癌细胞在体外和体内的迁移和肿瘤血管生成。重要的是，抑制 S100A4 可损害 OSX 诱导的细胞迁移和毛细血管样管形成。恢复 S100A4 的表达可挽救 OSX-shRNA 抑制的细胞迁移和毛细血管样管形成。此外，OSX 和 S100A4 的表达水平在人乳腺癌肿瘤中显著相关。我们的研究表明，OSX 作为细胞迁移和肿瘤血管生成的致癌驱动因子，可能成为人类乳腺癌治疗的潜在治疗靶点。
